Recent studies of healthy, male, New York homosexuals revealed that a substantial fraction have immunologic abnormalities similar to those observed in persons with clinical manifestations of Acquired Immunodeficiency Syndrome (AIDS), i.e. Kaposi's sarcoma (KS) or opportunistic infections (OI). Specifically, T helper to T suppressor lymphocyte (H/S) ratios were depressed and lymphocyte transformation to mitogen stimulation was impaired relative to heterosexual controls. Although inconclusive at this time, these findings suggest that a substantial number of mild or prodromal AIDS may be present in addition to the reported cases of KS and OI. The present research proposal is aimed at investigating the pathogenesis of AIDS, KS and OI and searching for sensitive and specific predictors of development of these diseases by means of a proposective study of a cohort of healthy male homosexuals. At enlistment each cohort member will undergo an interview, a physical examination, and skin testing. Blood for immunologic screening, blood count and serum storage will be obtained. Epidemiologic data obtained at enlistment will be analyzed for risk factors for immunologic abnormalities; survival data will be analyzed for risk factors for KS/OI. Subjects developing definitive AIDS will be recalled with appropriate controls and investigated to determine the relationships to disease of a number of viral and other antibodies in stored and current sera. In addition, intensive serial studies of a subset of 100 cohort members and 30 heterosexual controls will be performed. Studies will include viral cultures and serologies, interferon assay and detailed studies to evaluate B and T cell lymphocyte functions. These studies will be analyzed to elucidate the potential interrelationships of viral infections, abnormal immunologic parameters and other factors to the patheogenesis and etiology of AIDS.